The soluble extracellular domain (ECD) of a target receptor, such as the tumor necrosis factor receptor (TNFR), has therapeutic actions in human diseases. The receptor ECD acts as an exogenous decoy receptor, which sequesters the endogenous ligand, e.g. tumor necrosis factor (TNF)-α, and thereby blocks access of the endogenous ligand to the endogenous target receptor. Decoy receptors could be powerful new treatments of brain diseases. However, decoy receptors, like other large molecule drugs, do not cross the blood-brain barrier (BBB). Thus, to date, it has not been possible to treat patients with brain disorders by systemic administration of recombinant decoy receptors.